Schizophrenia remains one of the most disabling diseases in medicine. Interventions research is crucial for improving the lives of individuals who are at risk for, or who have developed this illness. Pharmacotherapy, coupled with psychosocial and rehabilitative treatment, continues to be essential. Functional outcomes remain disappointing, positive symptoms persist in many patients, and cognitive dysfunction and negative symptoms continue to be less treatment responsive than positive symptoms. Relapse is the rule, to the extent that repeated episodes are assumed to characterize the typical course of illness. Adverse effects remain a challenge, but the focus has shifted from neuromotor to metabolic adverse effects. Early phase illness stands out as an area with a great need for intervention research, providing a rich opportunity for an ACISR. We define early phase as those at risk for or within the first 5 years following diagnosis. Maximizing treatment effectiveness in early phase illness could have a profound impact on future course. Treatments for early phase patients have been tested mainly in chronic patients;the study of factors that predict response is likely to be more informative, with fewer confounds, in early phase illness. The overall goal of the proposed ACISR is to enhance investigator initiated science by providing infrastructure support to maximize research opportunities in three populations: Individuals experiencing prodromal signs and symptoms of schizophrenia;early onset schizophrenia, and first episode schizophrenia. The specific aims of our research efforts are to: 1) characterize the evolution of psychosis and identify targets for early intervention, 2) optimize interventions and outcomes in early phase illness, 3) assess, prevent, and minimize adverse effects of pharmacologic agents, 4) identify factors that predict treatment response. A key component of our proposed ACISR is to maintain and expand a research network consisting of non- academic, public and private community facilities, as well as local schools to enhance research opportunities and generalizability, as well as helping to improve levels of care in these programs. We believe that this ACISR would enable us to expand and extend our efforts in these valuable populations and to create a unique national resource. OPERATIONS CORE